CA1296868C - Process for preparing soluble and/or splitable tablets and tabletsthus obtained - Google Patents

Abstract

ABSTRACT

This invention relates to a process for the preparation of tablets readily soluble and/or splitable in water comprising introducing, into the preparation ready to be pressed, a sufficient amount of a liquid agent selected from within the halogenated hydrocarbons or mixtures thereof, proceeding with the compressing step and, finally, eliminating the volatile liquid which leads to a porous structure ; the invention relates also to tablets or analogs when produced according to the said process.

Description

The invention relates to a process for preparing readily soluble and/or splitable moulded compositions, such as tablets, and to the products thus obtained. Such tablets are useful in various cases such as, for instance, for sweeting agents (sugar or sugar substitutes) or for drugs.

Effervescent tablets and preparations are well ~nown forms of presentation of pharmaceutical specialities.
Generally, there is some delay in their dissolution or splitting. Moreover, effervescent tablets generally contain a 10 substantial amount of sodium usually in the form of sodium bicarbonate. The presence of sodium is preferably to be avoided for patients suffering from circulatory disorders and/or cardiac maladies. Various attempts to provide sodium free effervescent tablets without using freezing or lyophilisation techniques have, so far, not succeeded. The state of the art in this field may be exemplified by ~rench patent publications Nos. 2 199 973 and 2 335 205. The products obtained according to the first document are described as unsatisfactory by the second (page 2 lines 26-30). Indeed, it would be of special interest not merely to eliminate sodium from such tablets but to eliminate all metallic cations while retaining the property of rapid dissolution ar splitting in the presence of water.

The invention pxovides a process ~or the preparation of tablets readily soluble and/or splitable in water~ the process comprising introducing, into the preparation ready to be pressed or moulded, a sufficient amount of a liquid agent boiling between -35C and +50C, the agent being selected from within the halogenated hydrocarbons or mixtures thereof, proceeding with the moulding or compressing step and, finally, ~:~
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eliminating the volatile li~uid agent either slowly at room temperature or by gentle warming or by lowering the pressure or by both gentle warming and lowering of the pressure, with the proviso that the selected agent should be insoluble or poorly soluble in the components of the preparation to be moulded and should not react with or be firmly absorbed by the same.

The advantages of using a liquid which is practically a non-solvent of the components are the prevention of the sticking of the components to the mould and of a correlative deposit of the same and the possible suppression of a conventional lubricating agent due to the specific lubricating action of this liquid.

The selected agent should be introduced in the feeding device o~ the moulding unit or at any appropriate level in the mould.

The agent may be slowly eliminated at room temperature for agents boiling under the same or slightly over which - gives a product- with a porous structure ; if necessary, a moderate warming of the compressed products by any usual method and/or submitting them to a reduced pressure will be used.

Preferred volatile liquid agents are the non-flammable mono- or poly-halosubstituted hydrocarbons such as trichloro-fluoromethane, difluorochlorobromomethane, trichlorotrifluoro ethane, tetra~luorodichloroethane and dichloromethane or mixtures thereof.
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As the readily soluble and/or splitable tablets, obtained according to the invention, are generally dissolved and/or split very fast, the invention might also be used to speed the dissolution of conventional eff~rvescent tablets.

A particular advantage of the invention is that it can be performed easily in conventional tablet-moulding units fitted with appropriate extra means for injection of the agent and for its elimination with a possible recovering of the same in a drying step. This is a particularly strong advantage when it is considered that sophisticated freezing and warming equipments are needed to prepare readily soluble compositions by the lyophilisation methods.

The invention provides also the tablets or analogs obtained according to the a~orementioned process ; such tablets may easily be identified by the analytical identification of traces of the volatile agent used.

Some examples of preparations obtained according to the invention are given below.

EXAMPT~ 1 Sweetening tablets.

N-L-~-Aspartyl-L-phenylalanine methyl ester 0.020 g Lactose 0.280 g For one tablet ~inished at : 0.300 g Dichloromethane 0.4 ml Elimination at 60-70C for half an hour.

EXAMPLE 2 Sodium cyclamate tablets.

Sodium cyclamate 0.050 g Mannitol 0.350 g For one tablet finished at : 0.400 g Trichloro~luoromethane (Fll) 0.5 ml Elimination at 50~C about 40 minutes.

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EXAMPLE 3 Saccharin sodium tablets.

Saccharin sodium 0.010 g Lactose 0.190 g For one tablet finished at : 0.200 g ~ 5 Trichlorofluoromethane ~Fll) 0.1 ml ; ` ~
Elimination at room temperature ~or 25 minutes.

EXAMPLE 4 Monoammonium glycyrrhi2inate tablets.

Monoammonium glycyrrhizinate 0.050 g Mannitol 0.250 g ~`~ 10 Lactose 0.200 g For one tablet ~inished at 0.500 g Trichlorofluoromethane (Fl]) 0.2 ml Dichlorotetrafluoroethane tF114) 0.2 ml 0.4 ml ; 15 Elimination at 50C between 30 and 40 minutes.
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EXAMPLE 5 Betain Citrat 2 000 g Sodium bicarbonate 0.450 g - Citric anhydrous acid 0.050 g `~ Polyoxyethyleneglycol 6.000 0.060 g 20 Sodium saccharinate ~ 0.010 g Lemon flavour ~ 0.002 g Orange flavour 0.005 g Sorbitol l.OOO g ; MannLtol 2.423 g For one tablet finLshed at 6.000 g : ~ : :

Trichlorofluoromethane (Fll) 2.5 ml Elimination at room temperature for 12 hours.

EXaMPLE 6 Aluminium hydroxide and magnesium carbonate gel tablets.

Aluminium hydroxide and magnesium ; co-dried carbonate gel 0.300 g ~annitol 0.290 g Aspartame 0.010 g For one tablet finished at : 0.600 g Trichlorofluoromethane (Fll) 0.2 ml Trichlorotrifluoroethane (F113) 0.2 ml 0.4 ml Elimination at 60-70C for one hour.
i EXAMPLE 7 Acetylsalicylic acid tablets.

Acetylsalicylic acid 0.500 g Wheat starch 0.070 g Mannitol 0.230 g For one tablet finished at : 0.800 g Trichlorofluoromethane (Fll) 0.3 ml ichlorotetrafluoxoethane (F114) 0.1 ml ~ -- ~~ 0.4 ml Elimination- either at room temperature in about - 24h or at 50C in about five minutas (I.R.
warming).
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EXAMPLE 8 Ginkgo, heptaminol chlorhydrate and troxerutine extract soluble tablets.

Ginkgo ~iloba extract 0.014 g Heptaminol chorhydrate 0.300 g Troxerutine 0.300 g Silicic acid 0.002 g Polyoxyethyleneglycol 6.000 0.022 g Mannitol 0.262 g For one tablet finished at : 0.900 g Trichlorotrifluoroethane (F113) 0.5 ml Elimination at 60-70C for one hour ~XAMPLE ~ Smectite tablets.
;; Smectite 2.500 g Sodium saccharinate 0.010 g Mannitol 2.490 g For one tablet finished at : 5.000 g ~' ' Trichloro~luoromethane tFll) 1 ml Elimination at 50C for one hour~
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EXANPIE 10 Ginkgo extract soluble tablets.
; Ginkgo Biloba extract 0.040 g ; Mannitol 0.653 g Sodium saccharinate ~ 0.005 g - - Orange ~lavour ; 0.002 g .
For:one tablet ~1nished at : 0.700 g ~ Trichlorofluoromethane (Fll) 0.5 ml Elimination at room-temperature in about 24h or at 50C in about ~ive minutes (I.R warming).

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~ir,,8~3 EXAMPLE 11 Vitamine C soluble tablets.

Ascorbic acid 0.250 g Mannitol 0.350 g Monohydrated lactose 0.100 g For one tablet finished at : 0.700 g Trichlorotrifluoroethane (F113) 0.2 ml Dichlorotetrafluoroethane (F114) 0.2 ml 0.4 ml Elimination at 60-70C for one hour.

EXAMPLE 12 Vitamine C soluble tablets Ascorbic acid 0.100 g Mannitol 0.300 g For one tablet finished at : 0.400 g Trichlorotrifluoroethane (F113) 0.5 ml - Elimination at 60-70C for one hour.

EXAMPLE 13 Antiacid and absorbing tablets.

Montmorillonite 0.800 g Magnesium phosphate (S H20) 0.200 g For one tablet ~inishad at : 1.000 g Trichlorofluoromethane (FlI) 0.2 ml Dichlorotetrafluoroethane tF114) 0.2 ml - - 0.4 ml Elimination at 60--70C for one hour.

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6~8 EXAMPLE 14 Aluminium hydroxide and magnesium hydroxide tablets~

Aluminium hydroxide 0.250 g Magnesium hydroxide 0.250 g La~-tose 0.197 g Sorbitol 0.200 g Acide saccharinate 0.003 g For one tablet finished at : 0.900 g Dichloromethane 0.6 ml ~limination at 60-70C for one hour.

EXAMPLE 15 Ginkgolides tablets Ginkgolide A+B~C 0.040 g Lactose 0.260 g For one tablet finished at : 0.300 g Trichlorofluoromethane ~F11) 0.45 ml Elimination at room temperature in about 24h or at 50C in about five minutes (I.R warming).

E~aMPL~ 16 Bromomethyloxine tablets.

: ~ : Bromomethyloxine 0.033 g ~ 20 : ~ Colloidal silica 0.117 g . .
For one tablet finlshed~at : 0.150 g ~ ~ ~ Trichlorofluoromethane (Fli) 0.2 ml :
' Elimination at 50C fur half an hour.

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Claims (7)

1. A process for the preparation of tablets readily soluble and/or splitable in water comprising introducing, into the preparation ready to be pressed or moulded, a sufficient amount of a liquid agent boiling between -35°C and +50°C, the agent being selected from within the halogenated hydrocarbons or mixtures thereof, proceeding with the moulding or compressing step and, finally, eliminating the volatile liquid agent either slowly at room temperature or by gentle warming or by lowering the pressure or by both gentle warming and lowering of the pressure, with the proviso that the selected agent should be insoluble or poorly soluble in the components of the preparation to be moulded and should not react with or be firmly absorbed by the same.

2. The process of Claim 1, wherein the volatile liquid agent is a non-flammable mono- or poly-halosubstituted hydrocarbon or a mixture thereof.

3. The process of Claim 2, wherein the volatile liquid agent is trichlorofluoromethane, difluorochlorobromomethane, trichlorotrifluoroethane, tetrafluorodichloroethane, dichloromethane or a mixture thereof.

4. A tablet or analog when produced according to the process of Claims 1, 2 or 3.

5. A tablet or analog according to Claim 4, wherein traces of the volatile agent used in the process may be found.

6. A tablet or analog when produced according to the process of Claim 2.

7. A tablet or analog when produced according to the process of Claim 3.